JP2017512815A5 - - Google Patents

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JP2017512815A5
JP2017512815A5 JP2016560487A JP2016560487A JP2017512815A5 JP 2017512815 A5 JP2017512815 A5 JP 2017512815A5 JP 2016560487 A JP2016560487 A JP 2016560487A JP 2016560487 A JP2016560487 A JP 2016560487A JP 2017512815 A5 JP2017512815 A5 JP 2017512815A5
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さらに別の態様では、本発明は、腫瘍またはウイルス性疾患の治療における、本発明は記載されているような修飾Ｊ鎖を伴うＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭ、ＩｇＧ／ＩｇＡの抗体の使用に関する。
〔態様１〕修飾Ｊ鎖を含むＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体またはその抗原結合断片であって、該修飾Ｊ鎖がネイティブ配列のＪ鎖に導入される外来性の結合部分を含む、ＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体またはその抗原結合断片。
〔態様２〕ネイティブ配列のＪ鎖が、配列番号１のヒトのネイティブＪ鎖配列またはその機能的断片である、態様１のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様３〕ネイティブ配列のＪ鎖が、配列番号１のヒトのネイティブＪ鎖配列である、態様２のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様４〕外来性の結合部分が、直接的なまたは間接的な融合によって配列番号１のヒトのネイティブＪ鎖配列に導入される、態様３のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様５〕結合部分が、ペプチドリンカーを介した間接的な融合によって導入される、態様４のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様６〕間接的な融合が、結合部分のＣ末端及び／またはＮ末端にてまたはその近傍にてペプチドリンカーを介する、態様５のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様７〕外来性の結合部分が、Ｃ末端にてまたはその近傍にて配列番号１のヒトのネイティブＪ鎖配列に導入される、態様６のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様８〕外来性の結合部分が、Ｃ末端から約１０残基以内で配列番号１のヒトのネイティブＪ鎖配列に導入される、態様７のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様９〕外来性の結合部分が、Ｎ末端にてまたはその近傍にて配列番号１のヒトのネイティブＪ鎖配列に導入される、態様６のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様１０〕外来性の結合部分が、Ｎ末端から約１０アミノ酸残基以内で配列番号１のヒトのネイティブＪ鎖配列に導入される、態様９のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様１１〕外来性の結合部分が、配列番号１のシステイン残基９２と１０１の間でヒトのネイティブＪ鎖配列に導入される、態様５のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様１２〕外来性の結合部分が、グリコシル化部位にてまたはその近傍にて配列番号１のヒトのネイティブＪ鎖配列に導入される、態様５のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様１３〕前記ペプチドリンカーが約１０〜２０のアミノ酸の長さである、態様５のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様１４〕前記ペプチドリンカーが約１５〜２０のアミノ酸の長さである、態様１３のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様１５〕前記ペプチドリンカーが１５のアミノ酸の長さである、態様１４のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様１６〕外来性の結合部分が、化学的誘導体化または化学酵素的誘導体化によって配列番号１のヒトのネイティブＪ鎖配列に導入される、態様３のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様１７〕外来性の結合部分が、化学リンカーによって配列番号１のヒトのネイティブＪ鎖配列に導入される、態様１６のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様１８〕化学リンカーが切断可能なリンカーまたは切断可能ではないリンカーである、態様１７のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様１９〕切断可能なリンカーが化学的に不安定なリンカーまたは酵素に不安定なリンカーである、態様１８のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様２０〕リンカーが、Ｎ−スクシンイミジル−３−（２−ピリジルジチオ）プロピオネート（ＳＰＤＰ）、スクシンイミジル−４−（Ｎ−マレイミドメチル）シクロヘキサン−１−カルボキシレート（ＳＭＣＣ）、Ｎ−スクシンイミジル−４−（２−ピリジルチオ）ペンタノエート（ＳＰＰ）、イミノチオラン（ＩＴ）、イミドエステルの二官能性誘導体、活性エステル、アルデヒド、ビス−アジド化合物、ビス−ジアゾニウム誘導体、ジイソシアネート、及びビス−活性フッ素化合物から成る群から選択される、態様１８のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様２１〕酵素認識部位の挿入によって、及びペプチドリンカーまたは非ペプチドリンカーを介して該酵素認識部位にて外来性の結合部分を翻訳後に連結することによって修飾される、態様１６のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様２２〕外来性の結合部分が、抗体、抗体の抗原結合断片、抗体−薬剤コンジュゲート、抗体様分子、抗体様分子の抗原結合断片、可溶性タンパク質及び膜結合型タンパク質、リガンド、受容体、ウイルス様粒子、タンパク質毒素、酵素、及び代替足場から成る群から選択される、態様１〜２１のいずれかのＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様２３〕代替足場が、ダルピン、フィブロネクチンドメイン、アドネクチン及びノッティンから成る群から選択される、態様２２のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様２４〕抗原結合断片が、Ｆ（ａｂ’） ２ 、Ｆ（ａｂ） ２ 、Ｆａｂ’、Ｆａｂ、Ｆｖ、ｓｃＦｖ、及び単一ドメイン抗体から成る群から選択される、態様２２のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様２５〕抗原結合断片がｓｃＦｖである、態様２４のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様２６〕外来性の結合部分がエフェクター細胞に結合する、態様１〜２１のいずれかのＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様２７〕エフェクター細胞が、Ｔ細胞、ナチュラルキラー（ＮＫ）細胞、マクロファージ及び好中球から成る群から選択される、態様２６のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様２８〕エフェクター細胞がＴ細胞である、態様２７のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様２９〕外来性の結合部分がＴ細胞上のＣＤ３εに結合する、態様２８のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様３０〕エフェクター細胞がＮＫ細胞である、態様２７のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様３１〕外来性の結合部分が、ＮＫ細胞上のＣＤ１６、ＣＤ６４及びＮＫＧ２Ｄから成る群から選択される標的を結合する、態様３０のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様３２〕エフェクター細胞がマクロファージである、態様２７のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様３３〕外来性の結合部分が、マクロファージ上のＣＤ１４に結合する、態様３２のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様３４〕エフェクター細胞が好中球である、態様２７のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様３５〕外来性の結合部分が、好中球上のＣＤ１６ｂまたはＣＤ１７７に結合する、態様３４のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭまたはＩｇＧ／ＩｇＡ抗体。
〔態様３６〕ＩｇＭ抗体またはその抗原結合断片である、態様１の抗体。
〔態様３７〕ＩｇＡ抗体またはその抗原結合断片である、態様１の抗体。
〔態様３８〕単一特異性である、またはその抗原結合断片である、先行態様のいずれかの抗体。
〔態様３９〕二重特異性である、またはその抗原結合断片である、態様３８の抗体。
〔態様４０〕多重特異性である、またはその抗原結合断片である、態様３８の抗体。
〔態様４１〕修飾Ｊ鎖がＶ−リンカー−Ｊの方向である、態様１〜４０のいずれかの抗体。
〔態様４２〕修飾Ｊ鎖がＪ−リンカー−Ｖの方向である、態様１〜４０のいずれかの抗体。
〔態様４３〕前記抗体が、標的細胞、可溶性結合標的、細胞表面受容体、マトリックスタンパク質、及び輸送体受容体から成る群から選択される１以上の結合標的に対する結合特異性を有する、態様１〜４２のいずれかの抗体。
〔態様４４〕前記抗体が腫瘍細胞に結合する、態様１〜４２のいずれかの抗体。
〔態様４５〕前記抗体が、図１９に列挙された腫瘍標的関連抗原に結合する、態様１〜４２のいずれかの抗体。
〔態様４６〕Ｊ鎖が、図１９に列挙されたエフェクター細胞標的のいずれかを結合するように修飾される、態様４５の抗体。
〔態様４７〕腫瘍細胞が血液癌細胞または固形腫瘍細胞である、態様４４の抗体。
〔態様４８〕血液癌細胞が、白血病、リンパ腫、骨髄腫及び骨髄異形成症候群から成る群から選択される血液癌に由来する、態様４７の抗体。
〔態様４９〕白血病が、急性骨髄性白血病、急性リンパ芽球性白血病、慢性骨髄性白血病、または慢性リンパ性白血病である、態様４８の抗体。
〔態様５０〕リンパ腫が、ホジキンリンパ腫または非ホジキンリンパ腫である、態様４８の抗体。
〔態様５１〕前記抗体が、ＣＤＩＭ、ＣＤ１９、ＣＤ２０、ＣＤ２２、ＣＤ３３、ＣＤ７０、ＣＤ５６、ＣＤ１３８の１以上に結合する、態様４７の抗体。
〔態様５２〕修飾Ｊ鎖がＣＤ３εに結合する、態様５１の抗体。
〔態様５３〕抗体がＣＤ２０に結合し、修飾Ｊ鎖がＣＤ３εを結合する、態様５２の抗体。
〔態様５４〕固形腫瘍細胞が上皮癌に由来する、態様４７の抗体。
〔態様５５〕上皮癌が、胆嚢癌、乳癌、子宮頸癌、結腸直腸癌、子宮内膜癌、食道癌、胃癌、頭頚部の癌、肺癌、甲状腺髄様癌、腎癌、卵巣癌、膵臓癌、肝臓癌、前立腺癌、または膀胱癌である、態様５４の抗体。
〔態様５６〕固形腫瘍細胞が黒色腫腫瘍細胞である、態様４７の抗体。
〔態様５７〕固形腫瘍細胞が神経膠腫の腫瘍細胞である、態様４７の抗体。
〔態様５８〕抗体が腫瘍細胞上の糖質系標的に結合する、態様４４の抗体。
〔態様５９〕抗体がウイルス抗原に結合する、態様１〜４２のいずれかの抗体。
〔態様６０〕ウイルス抗原がＨＢＶ抗原またはＨＩＶ抗原である、態様５９の抗体。
〔態様６１〕ウイルス抗原がＰｒｅＳ１である、態様６０の抗体。
〔態様６２〕ウイルス抗原がＧＰ１２０である、態様６０の抗体。
〔態様６３〕先行態様のいずれかの前記抗体を含む、組成物。
〔態様６４〕さらに薬学上許容可能な担体を含む医薬組成物である、態様６３の組成物。
〔態様６５〕診断用組成物である、態様６３の組成物。
〔態様６６〕癌またはウイルス性疾患の治療方法であって、必要とする対象に有効量の態様１〜６２のいずれかの抗体を投与することを含む、治療方法。
〔態様６７〕癌またはウイルス性疾患の治療のための医薬の調製における態様１〜６２のいずれかの抗体の使用。
〔態様６８〕癌またはウイルス性疾患の治療における態様１〜６２のいずれかの抗体の使用。
〔態様６９〕ヒトのネイティブＪ鎖配列に導入される外来性の結合部分を含む修飾Ｊ鎖であって、ヒトのネイティブＪ鎖配列が配列番号１の配列またはその機能的断片を含み、外来性の結合部分が内部融合によってヒトのネイティブＪ鎖配列に導入される、修飾Ｊ鎖。
〔態様７０〕外来性の結合部分が、配列番号１のシステイン残基９２と１０１の間で内部融合によってヒトのネイティブＪ鎖配列に導入される、態様６９の修飾Ｊ鎖。
〔態様７１〕外来性の結合部分が、グリコシル化部位にてまたはその近傍にて内部融合によって配列番号１のヒトのネイティブＪ鎖配列に導入される、態様６９の修飾Ｊ鎖。
〔態様７２〕外来性の結合部分が、ペプチドリンカーを用いた内部融合によって配列番号１のヒトのネイティブＪ鎖配列に導入される、態様６９の修飾Ｊ鎖。
〔態様７３〕ペプチドリンカーが約１０〜２０のアミノ酸の長さである、態様７２の修飾Ｊ鎖。
〔態様７４〕ペプチドリンカーが約１５〜２０のアミノ酸の長さである、態様７３の修飾Ｊ鎖。
〔態様７５〕ペプチドリンカーが１５のアミノ酸の長さである、態様７４の修飾Ｊ鎖。
〔態様７６〕ヒトのネイティブＪ鎖配列に導入される外来性の結合部分を含む修飾Ｊ鎖であって、該ヒトのネイティブＪ鎖配列が配列番号１の配列またはその機能的断片を含み、該外来性の結合部分が化学的誘導体化または化学酵素的誘導体化によって該ヒトのネイティブＪ鎖配列に導入される、修飾Ｊ鎖。
〔態様７７〕外来性の結合部分が、化学リンカーによって配列番号１のヒトのネイティブＪ鎖配列に導入される、態様７６の修飾Ｊ鎖。
〔態様７８〕化学リンカーが切断可能なリンカーまたは切断可能ではないリンカーである、態様７７の修飾Ｊ鎖。
〔態様７９〕切断可能なリンカーが化学的に不安定なリンカーまたは酵素に不安定なリンカーである、態様７８の修飾Ｊ鎖。
〔態様８０〕リンカーが、Ｎ−スクシンイミジル−３−（２−ピリジルジチオ）プロピオネート（ＳＰＤＰ）、スクシンイミジル−４−（Ｎ−マレイミドメチル）シクロヘキサン−１−カルボキシレート（ＳＭＣＣ）、Ｎ−スクシンイミジル−４−（２−ピリジルチオ）ペンタノエート（ＳＰＰ）、イミノチオラン（ＩＴ）、イミドエステルの二官能性誘導体、活性エステル、アルデヒド、ビス−アジド化合物、ビス−ジアゾニウム誘導体、ジイソシアネート、及びビス−活性フッ素化合物から成る群から選択される、態様７９の修飾Ｊ鎖。
〔態様８１〕酵素認識部位の挿入によって、及びペプチドリンカーまたは非ペプチドリンカーを介して該酵素認識部位にて外来性の結合部分を翻訳後に連結することによって修飾される、態様７６の修飾Ｊ鎖。
〔態様８２〕外来性の結合部分が、抗体、抗体の抗原結合断片、抗体−薬剤コンジュゲート、抗体様分子、抗体様分子の抗原結合断片、可溶性タンパク質及び膜結合型タンパク質、リガンド、受容体、ウイルス様粒子、タンパク質毒素、酵素、及び代替足場から成る群から選択される、態様６９〜８１のいずれかの修飾Ｊ鎖。
〔態様８３〕代替足場が、ダルピン、フィブロネクチンドメイン、アドネクチン及びノッティンから成る群から選択される、態様８２の修飾Ｊ鎖。
〔態様８４〕抗原結合断片が、Ｆ（ａｂ’） ２ 、Ｆ（ａｂ） ２ 、Ｆａｂ’、Ｆａｂ、Ｆｖ、ｓｃＦｖ、及び単一ドメイン抗体から成る群から選択される、態様８２の修飾Ｊ鎖。
〔態様８５〕抗原結合断片がｓｃＦｖである、態様８４の修飾Ｊ鎖。
〔態様８６〕外来性の結合部分がエフェクター細胞に結合する、態様６９〜８１のいずれかの修飾Ｊ鎖。
〔態様８７〕エフェクター細胞が、Ｔ細胞、ナチュラルキラー（ＮＫ）細胞、マクロファージ及び好中球から成る群から選択される、態様８６の修飾Ｊ鎖。
〔態様８８〕エフェクター細胞がＴ細胞である、態様８７の修飾Ｊ鎖。
〔態様８９〕外来性の結合部分がＴ細胞上のＣＤ３εに結合する、態様８８の修飾Ｊ鎖。
〔態様９０〕エフェクター細胞がＮＫ細胞である、態様８７の修飾Ｊ鎖。
〔態様９１〕外来性の結合部分が、ＮＫ細胞上のＣＤ１６、ＣＤ６４及びＮＫＧ２Ｄから成る群から選択される標的を結合する、態様９０の修飾Ｊ鎖。
〔態様９２〕エフェクター細胞がマクロファージである、態様８７の修飾Ｊ鎖。
〔態様９３〕外来性の結合部分が、マクロファージ上のＣＤ１４に結合する、態様９２の修飾Ｊ鎖。
〔態様９４〕エフェクター細胞が好中球である、態様８７の修飾Ｊ鎖。
〔態様９５〕外来性の結合部分が、好中球上のＣＤ１６ｂまたはＣＤ１７７に結合する、態様９４の修飾Ｊ鎖。 In yet another aspect, the invention relates to the use of IgM, IgA, IgG / IgM, IgG / IgA antibodies with a modified J chain as described in the treatment of tumors or viral diseases.
[Aspect 1] An IgM, IgA, IgG / IgM or IgG / IgA antibody or antigen-binding fragment thereof containing a modified J chain, wherein the modified J chain is introduced into the native sequence J chain. IgM, IgA, IgG / IgM or IgG / IgA antibody or antigen-binding fragment thereof.
[Aspect 2] The IgM, IgA, IgG / IgM or IgG / IgA antibody of aspect 1, wherein the J chain of the native sequence is the human native J chain sequence of SEQ ID NO: 1 or a functional fragment thereof.
[Aspect 3] The IgM, IgA, IgG / IgM or IgG / IgA antibody of aspect 2, wherein the J chain of the native sequence is the human native J chain sequence of SEQ ID NO: 1.
[Aspect 4] The IgM, IgA, IgG / IgM or IgG / IgA antibody of aspect 3, wherein the exogenous binding moiety is introduced into the human native J chain sequence of SEQ ID NO: 1 by direct or indirect fusion .
[Aspect 5] The IgM, IgA, IgG / IgM or IgG / IgA antibody of aspect 4, wherein the binding moiety is introduced by indirect fusion via a peptide linker.
[Aspect 6] The IgM, IgA, IgG / IgM or IgG / IgA antibody of aspect 5, wherein the indirect fusion is via a peptide linker at or near the C-terminal and / or N-terminal of the binding moiety.
[Aspect 7] The IgM, IgA, IgG / IgM or IgG / IgA antibody of aspect 6, wherein the foreign binding moiety is introduced at or near the C-terminus into the human native J chain sequence of SEQ ID NO: 1 .
[Aspect 8] The IgM, IgA, IgG / IgM or IgG / IgA antibody of aspect 7, wherein the exogenous binding moiety is introduced into the human native J chain sequence of SEQ ID NO: 1 within about 10 residues from the C-terminus .
[Aspect 9] The IgM, IgA, IgG / IgM or IgG / IgA antibody of aspect 6, wherein the foreign binding moiety is introduced at or near the N-terminus into the human native J chain sequence of SEQ ID NO: 1 .
[Aspect 10] The IgM, IgA, IgG / IgM or IgG / IgA of aspect 9 wherein the foreign binding moiety is introduced into the human native J chain sequence of SEQ ID NO: 1 within about 10 amino acid residues from the N-terminus. antibody.
[Aspect 11] The IgM, IgA, IgG / IgM or IgG / IgA antibody of aspect 5, wherein the foreign binding moiety is introduced into the human native J chain sequence between cysteine residues 92 and 101 of SEQ ID NO: 1 .
[Aspect 12] The IgM, IgA, IgG / IgM or IgG / IgA of aspect 5 wherein the exogenous binding moiety is introduced into the human native J chain sequence of SEQ ID NO: 1 at or near the glycosylation site antibody.
[Aspect 13] The IgM, IgA, IgG / IgM or IgG / IgA antibody of aspect 5, wherein the peptide linker is about 10-20 amino acids in length.
[Aspect 14] The IgM, IgA, IgG / IgM or IgG / IgA antibody of aspect 13, wherein the peptide linker is about 15-20 amino acids in length.
[Aspect 15] The IgM, IgA, IgG / IgM or IgG / IgA antibody of aspect 14, wherein the peptide linker is 15 amino acids in length.
[Aspect 16] The IgM, IgA, IgG / IgM or IgG / of aspect 3 wherein the exogenous binding moiety is introduced into the human native J chain sequence of SEQ ID NO: 1 by chemical derivatization or chemoenzymatic derivatization. IgA antibody.
[Aspect 17] The IgM, IgA, IgG / IgM or IgG / IgA antibody of aspect 16, wherein the exogenous binding moiety is introduced into the human native J chain sequence of SEQ ID NO: 1 by a chemical linker.
[Aspect 18] The IgM, IgA, IgG / IgM or IgG / IgA antibody of Aspect 17, wherein the chemical linker is a cleavable linker or a non-cleavable linker.
[Aspect 19] The IgM, IgA, IgG / IgM or IgG / IgA antibody of Aspect 18, wherein the cleavable linker is a chemically labile linker or an enzyme labile linker.
[Aspect 20] The linker is N-succinimidyl-3- (2-pyridyldithio) propionate (SPDP), succinimidyl-4- (N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC), N-succinimidyl-4- From the group consisting of (2-pyridylthio) pentanoate (SPP), iminothiolane (IT), bifunctional derivatives of imide esters, active esters, aldehydes, bis-azide compounds, bis-diazonium derivatives, diisocyanates, and bis-active fluorine compounds The selected IgM, IgA, IgG / IgM or IgG / IgA antibody of aspect 18.
[Aspect 21] The IgM, IgA of aspect 16, which is modified by insertion of an enzyme recognition site and by post-translational linking of an exogenous binding moiety at the enzyme recognition site via a peptide linker or a non-peptide linker. IgG / IgM or IgG / IgA antibody.
[Aspect 22] The foreign binding moiety is an antibody, an antigen-binding fragment of an antibody, an antibody-drug conjugate, an antibody-like molecule, an antigen-binding fragment of an antibody-like molecule, a soluble protein and a membrane-bound protein, a ligand, a receptor, The IgM, IgA, IgG / IgM or IgG / IgA antibody of any of embodiments 1-21, selected from the group consisting of virus-like particles, protein toxins, enzymes, and alternative scaffolds.
[Aspect 23] The IgM, IgA, IgG / IgM or IgG / IgA antibody of aspect 22, wherein the alternative scaffold is selected from the group consisting of dalpine, fibronectin domain, adnectin and nottin.
[Aspect 24] The IgM, IgA of aspect 22, wherein the antigen-binding fragment is selected from the group consisting of F (ab ′) 2 , F (ab) 2 , Fab ′, Fab, Fv, scFv, and a single domain antibody. IgG / IgM or IgG / IgA antibodies.
[Aspect 25] The IgM, IgA, IgG / IgM or IgG / IgA antibody of aspect 24, wherein the antigen-binding fragment is scFv.
[Aspect 26] The IgM, IgA, IgG / IgM or IgG / IgA antibody of any one of Aspects 1-21, wherein the foreign binding moiety binds to effector cells.
[Aspect 27] The IgM, IgA, IgG / IgM or IgG / IgA antibody of Aspect 26, wherein the effector cells are selected from the group consisting of T cells, natural killer (NK) cells, macrophages and neutrophils.
[Aspect 28] The IgM, IgA, IgG / IgM or IgG / IgA antibody of aspect 27, wherein the effector cells are T cells.
[Aspect 29] The IgM, IgA, IgG / IgM or IgG / IgA antibody of aspect 28, wherein the foreign binding moiety binds to CD3ε on T cells.
[Aspect 30] The IgM, IgA, IgG / IgM or IgG / IgA antibody of aspect 27, wherein the effector cells are NK cells.
[Aspect 31] The IgM, IgA, IgG / IgM or IgG / IgA antibody of Aspect 30, wherein the exogenous binding moiety binds a target selected from the group consisting of CD16, CD64 and NKG2D on NK cells.
[Aspect 32] The IgM, IgA, IgG / IgM or IgG / IgA antibody of aspect 27, wherein the effector cells are macrophages.
[Aspect 33] The IgM, IgA, IgG / IgM or IgG / IgA antibody of aspect 32, wherein the foreign binding moiety binds to CD14 on macrophages.
[Aspect 34] The IgM, IgA, IgG / IgM or IgG / IgA antibody of aspect 27, wherein the effector cell is a neutrophil.
[Aspect 35] The IgM, IgA, IgG / IgM or IgG / IgA antibody of Aspect 34, wherein the foreign binding moiety binds to CD16b or CD177 on neutrophils.
[Aspect 36] The antibody of aspect 1, which is an IgM antibody or an antigen-binding fragment thereof.
[Aspect 37] The antibody according to Aspect 1, which is an IgA antibody or an antigen-binding fragment thereof.
[Aspect 38] The antibody according to any one of the preceding aspects, which is monospecific or an antigen-binding fragment thereof.
[Aspect 39] The antibody of aspect 38, which is bispecific or is an antigen-binding fragment thereof.
[Aspect 40] The antibody of aspect 38, which is multispecific or an antigen-binding fragment thereof.
[Aspect 41] The antibody according to any one of aspects 1 to 40, wherein the modified J chain is in the direction of V-linker-J.
[Aspect 42] The antibody according to any one of aspects 1 to 40, wherein the modified J chain is in the direction of J-linker-V.
[Aspect 43] The above antibody has binding specificity for one or more binding targets selected from the group consisting of target cells, soluble binding targets, cell surface receptors, matrix proteins, and transporter receptors. 42. The antibody of any one of 42.
[Aspect 44] The antibody according to any one of aspects 1 to 42, wherein the antibody binds to tumor cells.
[Aspect 45] The antibody according to any one of Aspects 1-42, wherein the antibody binds to a tumor target-related antigen listed in FIG.
[Aspect 46] The antibody of aspect 45, wherein the J chain is modified to bind any of the effector cell targets listed in FIG.
[Aspect 47] The antibody according to Aspect 44, wherein the tumor cell is a hematological cancer cell or a solid tumor cell.
[Aspect 48] The antibody of Aspect 47, wherein the hematological cancer cell is derived from a hematological cancer selected from the group consisting of leukemia, lymphoma, myeloma and myelodysplastic syndrome.
[Aspect 49] The antibody of Aspect 48, wherein the leukemia is acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, or chronic lymphocytic leukemia.
[Aspect 50] The antibody according to Aspect 48, wherein the lymphoma is Hodgkin lymphoma or non-Hodgkin lymphoma.
[Aspect 51] The antibody according to Aspect 47, wherein the antibody binds to one or more of CDIM, CD19, CD20, CD22, CD33, CD70, CD56, and CD138.
[Aspect 52] The antibody of Aspect 51, wherein the modified J chain binds to CD3ε.
[Aspect 53] The antibody of aspect 52, wherein the antibody binds to CD20 and the modified J chain binds CD3ε.
[Aspect 54] The antibody according to Aspect 47, wherein the solid tumor cells are derived from epithelial cancer.
[Aspect 55] The epithelial cancer is gallbladder cancer, breast cancer, cervical cancer, colorectal cancer, endometrial cancer, esophageal cancer, stomach cancer, head and neck cancer, lung cancer, medullary thyroid cancer, renal cancer, ovarian cancer, pancreas The antibody of embodiment 54, wherein the antibody is cancer, liver cancer, prostate cancer, or bladder cancer.
[Aspect 56] The antibody according to Aspect 47, wherein the solid tumor cells are melanoma tumor cells.
[Aspect 57] The antibody according to Aspect 47, wherein the solid tumor cell is a glioma tumor cell.
[Aspect 58] The antibody of aspect 44, wherein the antibody binds to a carbohydrate target on tumor cells.
[Aspect 59] The antibody according to any one of aspects 1 to 42, wherein the antibody binds to a viral antigen.
[Aspect 60] The antibody according to Aspect 59, wherein the viral antigen is HBV antigen or HIV antigen.
[Aspect 61] The antibody of Aspect 60, wherein the viral antigen is PreS1.
[Aspect 62] The antibody according to Aspect 60, wherein the viral antigen is GP120.
[Aspect 63] A composition comprising the antibody according to any one of the preceding aspects.
[Aspect 64] The composition of Aspect 63, which is a pharmaceutical composition further comprising a pharmaceutically acceptable carrier.
[Aspect 65] The composition according to Aspect 63, which is a diagnostic composition.
[Aspect 66] A method for treating cancer or a viral disease, comprising administering an effective amount of the antibody according to any one of aspects 1 to 62 to a subject in need thereof.
[Aspect 67] Use of the antibody according to any one of Aspects 1 to 62 in the preparation of a medicament for the treatment of cancer or viral diseases.
[Aspect 68] Use of the antibody according to any one of Aspects 1 to 62 in the treatment of cancer or viral diseases.
[Aspect 69] A modified J chain comprising a foreign binding moiety introduced into a human native J chain sequence, wherein the human native J chain sequence comprises the sequence of SEQ ID NO: 1 or a functional fragment thereof, A modified J chain in which the binding moiety is introduced into the native human J chain sequence by internal fusion.
[Aspect 70] A modified J chain according to aspect 69, wherein the exogenous binding moiety is introduced into the human native J chain sequence by internal fusion between cysteine residues 92 and 101 of SEQ ID NO: 1.
[Aspect 71] The modified J chain of aspect 69, wherein the exogenous binding moiety is introduced into the human native J chain sequence of SEQ ID NO: 1 by internal fusion at or near the glycosylation site.
[Aspect 72] The modified J chain according to Aspect 69, wherein the exogenous binding moiety is introduced into the human native J chain sequence of SEQ ID NO: 1 by internal fusion using a peptide linker.
[Aspect 73] The modified J chain of Aspect 72, wherein the peptide linker is about 10-20 amino acids in length.
[Aspect 74] The modified J chain of aspect 73, wherein the peptide linker is about 15-20 amino acids in length.
[Aspect 75] The modified J chain of aspect 74, wherein the peptide linker is 15 amino acids in length.
[Aspect 76] A modified J chain comprising an exogenous binding moiety introduced into a human native J chain sequence, wherein the human native J chain sequence comprises the sequence of SEQ ID NO: 1 or a functional fragment thereof, A modified J chain in which an exogenous binding moiety is introduced into the human native J chain sequence by chemical or chemoenzymatic derivatization.
[Aspect 77] The modified J chain of aspect 76, wherein the exogenous binding moiety is introduced into the human native J chain sequence of SEQ ID NO: 1 by a chemical linker.
[Aspect 78] The modified J chain according to Aspect 77, wherein the chemical linker is a cleavable linker or a non-cleavable linker.
[Aspect 79] The modified J chain according to Aspect 78, wherein the cleavable linker is a chemically labile linker or an enzyme labile linker.
[Aspect 80] The linker is N-succinimidyl-3- (2-pyridyldithio) propionate (SPDP), succinimidyl-4- (N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC), N-succinimidyl-4- From the group consisting of (2-pyridylthio) pentanoate (SPP), iminothiolane (IT), bifunctional derivatives of imide esters, active esters, aldehydes, bis-azide compounds, bis-diazonium derivatives, diisocyanates, and bis-active fluorine compounds The modified J chain of embodiment 79, which is selected.
[Aspect 81] The modified J chain according to Aspect 76, which is modified by insertion of an enzyme recognition site and by post-translational ligation of an exogenous binding moiety at the enzyme recognition site via a peptide linker or a non-peptide linker.
[Aspect 82] The foreign binding moiety is an antibody, an antigen-binding fragment of an antibody, an antibody-drug conjugate, an antibody-like molecule, an antigen-binding fragment of an antibody-like molecule, a soluble protein and a membrane-bound protein, a ligand, a receptor, The modified J chain of any of aspects 69-81, selected from the group consisting of virus-like particles, protein toxins, enzymes, and alternative scaffolds.
[Aspect 83] The modified J chain of aspect 82, wherein the alternative scaffold is selected from the group consisting of dalpine, fibronectin domain, adnectin and nottin.
[Aspect 84] The modified J chain of aspect 82, wherein the antigen-binding fragment is selected from the group consisting of F (ab ′) 2 , F (ab) 2 , Fab ′, Fab, Fv, scFv, and a single domain antibody. .
[Aspect 85] The modified J chain according to Aspect 84, wherein the antigen-binding fragment is scFv.
[Aspect 86] The modified J chain according to any one of aspects 69 to 81, wherein the exogenous binding moiety binds to an effector cell.
[Aspect 87] The modified J chain according to Aspect 86, wherein the effector cells are selected from the group consisting of T cells, natural killer (NK) cells, macrophages and neutrophils.
[Aspect 88] The modified J chain according to Aspect 87, wherein the effector cell is a T cell.
[Aspect 89] The modified J chain according to Aspect 88, wherein the exogenous binding moiety binds to CD3ε on T cells.
[Aspect 90] The modified J chain according to Aspect 87, wherein the effector cells are NK cells.
[Aspect 91] The modified J chain according to Aspect 90, wherein the exogenous binding moiety binds a target selected from the group consisting of CD16, CD64 and NKG2D on NK cells.
[Aspect 92] The modified J chain according to Aspect 87, wherein the effector cell is a macrophage.
[Aspect 93] The modified J chain according to Aspect 92, wherein the exogenous binding moiety binds to CD14 on macrophages.
[Aspect 94] The modified J chain according to Aspect 87, wherein the effector cell is a neutrophil.
[Aspect 95] The modified J chain according to Aspect 94, wherein the exogenous binding moiety binds to CD16b or CD177 on neutrophils.

Claims (20)

修飾Ｊ鎖を含むＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭ若しくはＩｇＧ／ＩｇＡ抗体またはその抗原結合断片であって、該修飾Ｊ鎖がネイティブ配列のＪ鎖に導入される外来性の結合部分を含む、ＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭ若しくはＩｇＧ／ＩｇＡ抗体またはその抗原結合断片。 An IgM, IgA, IgG / IgM or IgG / IgA antibody or antigen-binding fragment thereof comprising a modified J chain, wherein the modified J chain comprises a foreign binding moiety introduced into the native sequence J chain, IgA, IgG / IgM or IgG / IgA antibody or antigen-binding fragment thereof. ネイティブ配列のＪ鎖が、配列番号１のヒトのネイティブＪ鎖配列またはその機能的断片である、請求項１に記載のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭ若しくはＩｇＧ／ＩｇＡ抗体またはその抗原結合断片。 The IgM, IgA, IgG / IgM or IgG / IgA antibody or antigen-binding fragment thereof according to claim 1, wherein the J chain of the native sequence is the human native J chain sequence of SEQ ID NO: 1 or a functional fragment thereof . 外来性の結合部分が、直接的なまたは間接的な融合によって配列番号１のヒトのネイティブＪ鎖配列に導入されるポリペプチドである、請求項１または２に記載のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭ若しくはＩｇＧ／ＩｇＡ抗体またはその抗原結合断片。 3. IgM, IgA, IgG / IgM according to claim 1 or 2 , wherein the exogenous binding moiety is a polypeptide introduced into the human native J chain sequence of SEQ ID NO: 1 by direct or indirect fusion. Alternatively, an IgG / IgA antibody or antigen-binding fragment thereof . 外来性の結合部分が、該外来性の結合部分のＣ末端及び／またはＮ末端に融合したペプチドリンカーを介する間接的な融合によって導入され、および該ペプチドリンカーが、約１０〜２０のアミノ酸の長さである、請求項３に記載のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭ若しくはＩｇＧ／ＩｇＡ抗体またはその抗原結合断片。 Binding portion of the exogenous is introduced by indirect fusion via a peptide linker fused to the C-terminus and / or N-terminus of the binding portion of the exogenous, and the peptide linker of about 10 to 20 amino acids in length is the, IgM according to claim 3, IgA, IgG / IgM or IgG / IgA antibody or antigen binding fragment thereof. 外来性の結合部分が、配列番号１のヒトのネイティブＪ鎖配列のＣ末端および／若しくはＮ末端の位置に、またはＣ末端および／若しくはＮ末端から約１０アミノ酸残基以内に導入される、請求項３または４に記載のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭ若しくはＩｇＧ／ＩｇＡ抗体またはその抗原結合断片。 Binding portion of exogenously, the position of the C-terminal and / or N-terminus of the native J chain sequence of SEQ ID NO: 1 human, or C-terminal and / or introduced within the N-terminal about 10 amino acid residues, wherein Item 5. The IgM, IgA, IgG / IgM or IgG / IgA antibody or antigen-binding fragment thereof according to Item 3 or 4 . 外来性の結合部分が、配列番号１のシステイン残基９２と１０１の間でヒトのネイティブＪ鎖配列に導入される、請求項３または４に記載のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭ若しくはＩｇＧ／ＩｇＡ抗体またはその抗原結合断片。 The IgM, IgA, IgG / IgM or IgG / IgA of claim 3 or 4 , wherein the exogenous binding moiety is introduced into the human native J chain sequence between cysteine residues 92 and 101 of SEQ ID NO: 1. An antibody or antigen-binding fragment thereof . 外来性の結合部分が、配列番号１のヒトのネイティブＪ鎖配列のグリコシル化部位にまたはその近傍に導入される、請求項３または４に記載のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭ若しくはＩｇＧ／ＩｇＡ抗体またはその抗原結合断片。 Binding portion of exogenously was or the glycosylation sites of native J chain sequence of human SEQ ID NO: 1 is introduced in the vicinity, IgM according to claim 3 or 4, IgA, IgG / IgM or IgG / IgA antibody or antigen-binding fragment thereof . 外来性の結合部分が、化学的誘導体化または化学酵素的誘導体化により、任意で切断可能なリンカーまたは切断可能ではないリンカーにより配列番号１のヒトのネイティブＪ鎖配列に導入され、該切断可能なリンカーが、任意で化学的に不安定なリンカーまたは酵素に不安定なリンカーであり、および該切断可能なリンカーまたは切断可能ではないリンカーが、任意でＮ−スクシンイミジル−３−（２−ピリジルジチオ）プロピオネート（ＳＰＤＰ）、スクシンイミジル−４−（Ｎ−マレイミドメチル）シクロヘキサン−１−カルボキシレート（ＳＭＣＣ）、Ｎ−スクシンイミジル−４−（２−ピリジルチオ）ペンタノエート（ＳＰＰ）、イミノチオラン（ＩＴ）、イミドエステルの二官能性誘導体、活性エステル、アルデヒド、ビス−アジド化合物、ビス−ジアゾニウム誘導体、ジイソシアネート、及びビス−活性フッ素化合物から成る群から選択される、請求項１または２に記載のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭ若しくはＩｇＧ／ＩｇＡ抗体またはその抗原結合断片。 An exogenous binding moiety is introduced into the human native J chain sequence of SEQ ID NO: 1 by chemical or chemoenzymatic derivatization, optionally with a cleavable linker or a non-cleavable linker, which is cleavable The linker is optionally a chemically labile linker or an enzyme labile linker, and the cleavable or non- cleavable linker is optionally N-succinimidyl-3- (2-pyridyldithio) Propionate (SPDP), succinimidyl-4- (N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC), N-succinimidyl-4- (2-pyridylthio) pentanoate (SPP), iminothiolane (IT), imide ester Functional derivatives, active esters, aldehydes, bis-azis Compounds, bis - diazonium derivatives, diisocyanates, and bis - is selected from the group consisting of active fluorine compounds, IgM according to claim 1 or 2, IgA, IgG / IgM or IgG / IgA antibody or antigen binding fragment thereof. 修飾Ｊ鎖が、酵素認識部位の挿入によって、及びペプチドリンカーまたは非ペプチドリンカーを介して該酵素認識部位にて外来性の結合部分を翻訳後に連結することによって修飾される、請求項８に記載のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭ若しくはＩｇＧ／ＩｇＡ抗体またはその抗原結合断片。 Modified J chain, by the insertion of the enzyme recognition site, and is modified by linking post-translationally the union of exogenous at the enzyme recognition site through a peptide linker or a non-peptide linker of claim 8 IgM, IgA, IgG / IgM or IgG / IgA antibody or antigen-binding fragment thereof . 外来性の結合部分が、抗体；Ｆ（ａｂ’） ２ 、Ｆ（ａｂ） ２ 、Ｆａｂ’、Ｆａｂ、Ｆｖ、及びｓｃＦｖから成る群から選択される抗体の抗原結合断片；抗体−薬剤コンジュゲート；抗体様分子；可溶性タンパク質；リガンド；受容体；ウイルス様粒子；タンパク質毒素；酵素；ならびにダルピン、フィブロネクチンドメイン、アドネクチン及びノッティンから成る群から選択される代替足場、から成る群から選択される、請求項１乃至９のいずれか一項に記載のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭ若しくはＩｇＧ／ＩｇＡ抗体またはその抗原結合断片。 An antigen-binding fragment of an antibody, wherein the foreign binding moiety is an antibody ; F (ab ′) 2 , F (ab) 2 , Fab ′, Fab, Fv, and scFv ; an antibody-drug conjugate ; antibody-like molecules; soluble protein; ligand; receptor; virus-like particle; protein toxins; enzymes; and DARPins, fibronectin domain, alternative scaffold selected from the group consisting of adnectin and knottin is selected from the group consisting of, claims The IgM, IgA, IgG / IgM or IgG / IgA antibody or antigen-binding fragment thereof according to any one of 1 to 9 . 外来性の結合部分が、Ｔ細胞、ナチュラルキラー（ＮＫ）細胞、マクロファージ及び好中球から成る群から選択されるエフェクター細胞に結合する、請求項１乃至１０のいずれか一項に記載のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭ若しくはＩｇＧ／ＩｇＡ抗体またはその抗原結合断片。 The IgM according to any one of claims 1 to 10, wherein the exogenous binding moiety binds to an effector cell selected from the group consisting of T cells, natural killer (NK) cells, macrophages and neutrophils, IgA, IgG / IgM or IgG / IgA antibody or antigen-binding fragment thereof . エフェクター細胞が、Ｔ細胞であり、および外来性の結合部分が、Ｔ細胞上のＣＤ３εに結合する、請求項１１に記載のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭ若しくはＩｇＧ／ＩｇＡ抗体またはその抗原結合断片。 Effector cells are T cells, and the binding portion of the exogenous binds to CD3ε on T cells, IgM according to claim 11, IgA, IgG / IgM or IgG / IgA antibody or antigen binding fragment thereof. エフェクター細胞が、ＮＫ細胞であり、および外来性の結合部分が、ＮＫ細胞上のＣＤ１６、ＣＤ６４及びＮＫＧ２Ｄから成る群から選択される標的に結合する、請求項１１に記載のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭ若しくはＩｇＧ／ＩｇＡ抗体またはその抗原結合断片。 Effector cells are NK cells, and the binding portion of the exogenous binds to a target selected from the group consisting of CD16, CD64 and NKG2D on NK cells, IgM according to claim 11, IgA, IgG / IgM or IgG / IgA antibody or antigen-binding fragment thereof . 修飾Ｊ鎖が、複数の外来性の結合部分を含む、請求項１乃至１３のいずれか一項に記載のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭ若しくはＩｇＧ／ＩｇＡ抗体またはその抗原結合断片。 The IgM, IgA, IgG / IgM or IgG / IgA antibody or antigen-binding fragment thereof according to any one of claims 1 to 13 , wherein the modified J chain comprises a plurality of exogenous binding moieties . 二重特異性または多重特異性である、請求項１乃至１４のいずれか一項に記載のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭ若しくはＩｇＧ／ＩｇＡ抗体またはその抗原結合断片。 The IgM, IgA, IgG / IgM or IgG / IgA antibody or antigen-binding fragment thereof according to any one of claims 1 to 14 , which is bispecific or multispecific . 血液癌細胞または固形腫瘍細胞に結合する、請求項１乃至１５のいずれか一項に記載のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭ若しくはＩｇＧ／ＩｇＡ抗体またはその抗原結合断片。 Binding to blood Ekigan cells or solid tumor cells, IgM according to any one of claims 1 to 15, IgA, IgG / IgM or IgG / IgA antibody or antigen binding fragment thereof. ウイルス抗原に結合する、請求項１乃至１５のいずれか一項に記載のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭ若しくはＩｇＧ／ＩｇＡ抗体またはその抗原結合断片。 Virus binds to an antigen, IgM according to any one of claims 1 to 15, IgA, IgG / IgM or IgG / IgA antibody or antigen binding fragment thereof. 修飾Ｊ鎖上の外来性の結合部分が、ＣＤ３εに結合する、請求項１６または１７に記載のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭ若しくはＩｇＧ／ＩｇＡ抗体またはその抗原結合断片。 The IgM, IgA, IgG / IgM or IgG / IgA antibody or antigen-binding fragment thereof according to claim 16 or 17 , wherein the exogenous binding moiety on the modified J chain binds to CD3ε. 請求項１乃至１８のいずれか一項に記載のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭ若しくはＩｇＧ／ＩｇＡ抗体またはその抗原結合断片、ならびに薬学上許容可能な担体を含む組成物。 IgM according to any one of claims 1 to 18, IgA, IgG / IgM or IgG / IgA antibody or antigen binding fragment thereof, as well as a set Narubutsu comprising a pharmaceutically acceptable carrier. 癌またはウイルス性疾患の治療における使用のための、請求項１乃至１８のいずれか一項に記載のＩｇＭ、ＩｇＡ、ＩｇＧ／ＩｇＭ若しくはＩｇＧ／ＩｇＡ抗体若しくはその抗原結合断片または請求項１９に記載の組成物。 For use in the treatment of cancer or viral disease, according to any one of claims 1 to 18 IgM, IgA, according to IgG / IgM or IgG / IgA antibody or antigen-binding fragment or claim 19 that Composition .
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